Do children with primary nocturnal enuresis have a retarded bone age? A cross‐sectional study

OBJECTIVE: Nocturnal enuresis is a common pediatric problem, the etiology of which is unclear. In recent years, various studies have been published stating that children with nocturnal enuresis exhibit growth and skeletal maturation retardation. METHODS: In this cross-sectional study, we included 27 patients (16 boys, 11 girls) between the ages of 6 and 14 years who had presented with primary nocturnal enuresis (PNE) complaints. We included in the evaluation 19 healthy subjects (12 boys, 7 girls), who were the siblings of the children with PNE, as the control group. RESULTS: The patients in both groups were similar in chronological age, bone age, height and weight, with no significant difference between groups (P>0.05). CONCLUSION: The two groups in our study consisted of the same genetic background. Thus, our results were found to be different from the previous studies. We have concluded that there is no direct relationship between enuresis nocturnal and skeletal maturation.     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

THE IMPACT OF PRE-CLERKING CLINICS ON SURGICAL OPERATION CANCELLATIONS: A PROSPECTIVE AUDIT

Pre-clerking of all patients undergoing elective general surgical operations was introduced at our hospital in an attempt to reduce an unacceptably high operation cancellation rate. A prospective audit has been performed on the effect of this policy on the cancellation rate. Before the introduction of pre-clerking there was a marked seasonal variation in the number of patients who failed to attend for surgery, which could be explained by absence on holiday. This seasonal variation disappeared after the start of pre-clerking clinics, but there has been no reduction in the number of cancellations for medical reasons.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Heterogeneity of clara cell glutathione. A possible basis for differences in cellular responses to pulmonary cytotoxicants

Clara-cell populations show a high degree of variation in susceptibility to injury by bioactivated cytotoxicants. Because glutathione (GSH) is critical for detoxification of electrophilic metabolites, heterogeneity in Clara cell GSH levels may lead to a wide range of cytotoxic responses. This study was designed to define the distinct GSH pools within Clara cells, characterize heterogeneity within the population, and examine whether heterogeneity contributes to susceptibility. Using fluorescent imaging combined with high-performance liquid chromatography analysis, semiquantitative measurements were obtained by evaluation of GSH using monochlorobimane and monobromobimane. In steady-state conditions, the GSH measured in isolated cells was in the femtomole range, but varied 4-fold between individual cells. Clara cells analyzed in situ and in vitro confirmed this heterogeneity. The response of these cells to compounds that modulate GSH was also variable. Diethylmaleate depleted GSH, whereas GSH monoethylester augmented it. However, both acted nonuniformly in isolated Clara cells. The depletion of intracellular GSH caused a striking decrease in cell viability upon incubation with naphthalene (NA). The sulfhydryl-binding fluorochrome BODIPY, which colocalized with tetramethylrosamine, a mitochondrial dye, demonstrated by confocal microscopy that cellular sulfhydryls are highest in the mitochondria, next-highest in cytoplasm, and lowest in the nucleus. These pools responded differently to modulators of GSH. We concluded that the steady-state intracellular GSH of Clara cells exists in distinct pools and is highly heterogeneous within the population, and that the heterogeneity of GSH levels corresponds closely to the response of Clara cells to injury by NA.     

Ameliorating effect of microdoses of a potentized homeopathic drug,Arsenicum Album,on arsenic-induced toxicity in mice

Background  

Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols.     

A mathematical model of optimized radioiodine-131 therapy of Graves' hyperthyroidism

Background

The current status of radioiodine-131 (RaI) dosimetry for Graves' hyperthyroidism is not clear. Recurrent hyperthyroidism and iatrogenic hypothyroidism are two problems which interact such that trying to solve one leads to exacerbation of the other. Optimized RaI therapy has therefore begun to be defined just in terms of early hypothyroidism (ablative therapy) as physicians have given up on reducing hypothyroidism.

Methods

Optimized therapy is evaluated both in terms of the greatest separation of cure rate from hypothyroidism rate (non-ablative therapy) or in terms of early hypothyroidism (ablative therapy) by mathematical modeling of outcome after radioiodine and critically discussing the three common methods of RaI dosing for Graves' disease.

Results

Cure follows a logarithmic relationship to activity administered or absorbed dose, while hypothyroidism follows a linear relationship. The effect of including or omitting factors in the calculation of the administered I–131 activity such as the measured thyroid uptake and effective half-life of RaI or giving extra compensation for gland size is discussed.

Conclusions

Very little benefit can be gained by employing complicated methods of RaI dose selection for non-ablative therapy since the standard activity model shows the best potential for cure and prolonged euthyroidism. For ablative therapy, a standard MBq/g dosing provides the best outcome in terms of cure and early hypothyroidism.